We report the prenatal diagnosis of cystic hygroma that was subsequently identified to have haploinsufficiency of the FOXF1 and FOXC2 genes via array comparative genomic hybridization (aCGH). Deletion o f these genes has previously neither been associated with cystic hygroma nor prenatally diagnosed. The FOX gene cluster is involved in cardiopulmonary development. This case expands the phenotypic spectrum o f abnormalities of the FOXF1 and FOXC2 genes, as it seems within the spectrum of function that disruption of the FOX gene cluster would lead to include abnormalities of prenatal onset. Identification of this association would not be possible with conventional karyotype or targeted aCGH. This case highlights the power of whole genomic aCGH to further delineate the etiology of birth defects.

Pelizaeus-Merzbacher disease (PMD) is neurodegenerative leukodystrophy caused by dysfunction of the proteolipid protein 1 (PLP1) gene on Xq22, which codes for an essential myelin protein. As an X-linked condition, PMD primarily affects males; however there have been a small number of affected females reported in the medical literature with a variety of different mutations in this gene. No affected females to date have a deletion like our patient. In addition to this, our patient has skewed X chromosome inactivation which adds to her presentation as her unaffected mother also carries the mutation.

Grange syndrome comprises arterial stenoses with hypertension, brachysyndactyly, bone fragility, learning disability, and cardiac defects. To date, we know of two reported families with five affected individuals. We report on one of the youngest cases, in a third family, a 3-year-old girl with brachysyndactyly, renal artery stenosis with hypertension, and bone fragility. She does not have apparent cardiac disease, suggesting cardiac anomalies may not be an obligatory finding in this syndrome.

We describe the clinical and cytogenetic findings in a female infant with partial trisomy 11q, Robin sequence, cardiac anomalies, and other minor malformations. We compare the phenotypic similarities of our case to a series by Pihko et al. (1981), who reported on 20 cases with partial trisomy 11q with similar associated craniofacial and cardiac defects. We conclude that genetic etiologies for patients diagnosed with the Robin sequence may be more common than previously believed and that initial karyotyping should be performed to aid both diagnosis and clinical management. In addition, the pattern of Robin sequence and cardiac defects may be specifically suggestive of partial trisomy 11q.

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